This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project is focused on understanding the interaction between human and picornaviral proteins. Picornaviruses are non-enveloped, single-stranded, positive polarity RNA viruses that cause many important human and animal diseases, including polio, hepatitis A, foot-and-mouth disease, and the common cold (rhinovirus). Although much work has gone into understanding the targets of the six nonstructural genes of polio in regards to the mechanism of replication and host-translational shut-off, very little is known about the binding targets of other picornaviruses. We are particularly interested in novel picornaviruses such as klassevirus, and are comparing host-virus protein interactions in this system with better characterized picornaviruses such as polio, as well as more divergent members of the picornavirus family such as Hepatitis A, and Coxsackievirus. To this end, we are using affinity purification of virus proteins expressed in human 293 cells to capture protein-interaction complexes, followed by LC-MS/MS analysis. Such work could help explain difference in virulence, replication, translation, and tropism between divergent members of the picornavirus family.